Chronic pain: pharmacologic treatment (Proceedings)

Acute pain has an initial biological purpose in that it initiates a protective withdrawal reflex when a painful stimulus is encountered so that the tissue damage is minimized. Because of its usefulness, acute pain is often called 'physiologic pain'. Unfortunately, unlike acute pain, chronic pain serves no biological purpose. The International Association for the Study of Pain (IASP) defines chronic pain this way, 'chronic pain has been defined as pain without apparent biological value'. And the American Pain Society states, 'chronic pain is pain without apparent biological value that has simply persisted or persisted beyond normal tissue healing time'. There is no protective aspect to chronic pain, in fact, one of the enigmas of chronic pain is that it can persist in the absence of the original pain-inciting injury or disease. This leads to difficulty in both determining the origin of, and initiating appropriate treatment for, chronic pain. As described in the book, 'Integrative Pain Medicine', 'Acute pain, however, may be readily contrasted with chronic pain. Acute pain usually occurs with tissue injury or disease. The value of acute pain perception arising from tissue damage in muscles, ligaments or nerves is obvious; it is a warning of imminent danger. Chronic pain, however, typically has no survival value … and often occurs in the absence of identifiable tissue damage; it is itself a disorder of the anatomy and function of the central nervous system.' Because of this lack of biological value, chronic pain is often referred to as 'pathological pain'. Unfortunately, the effects of chronic pain extend beyond the pain itself and untreated pain has a negative medical impact.

Furthermore, chronic pain can be extremely difficult to treat, especially certain types of chronic pain like pain of malignancy and neuropathic pain. Patients in chronic pain generally require higher dosages of analgesic drugs than patients with acute pain and are more likely to require multimodal analgesia and the use of drugs that are not traditionally considered analgesics. And, in spite of aggressive treatment, many human patients in chronic pain state that their pain is actually never successfully relieved.

Chronic pain as a disease

Untreated pain causes physical and physiologic changes in both the peripheral and central nervous system and these changes perpetuate the pain state in both animals and humans. These changes include peripheral sensitization, central sensitization, increased sympathetic innervation of dorsal root ganglia, disinhibition of inhibitory modulation, redistribution of nociceptive receptors in the laminae of the spinal cord, altered phenotype of damaged sensory nerve fibers and neuroreceptors, altered patterns of spinal cord interneuronal communication and changes in the gray matter of the brain. Chronic pain causes changes in the pain pathway that result in the continued presence of pain even in absence of an inciting cause, the amplification of pain signals, an exaggerated pain sensation in response to a lightly painful stimulus (hyperalgesia), the presence of pain in response to a nonpainful stimulus (allodynia) and a myriad of other changes that can result in symptomatic responses like anorexia, insomnia, hypertension, GI ulceration, etc… Because of the physiological (and psychological – at least in humans) changes brought about by chronic pain states, chronic pain has been defined as a disease rather than just a symptom of a disease. This is an important distinction since physicians are more likely to treat a disease than they are to treat a symptom.

The impact of chronic pain on humans and animals

The impact of chronic pain on humans can initially be described by hard numbers and cold facts. One of the most common reasons people seek medical care is pain, and chronic pain affects an estimated 76.2 million people in the United States, which means that chronic pain affects more people than diabetes, heart disease, and cancer combined. More than $100 billion is spent in the US each year for pain related medical costs, lost income, and lost productivity.

So how does this equate to what happens in veterinary patients? Although companion animals like dogs and cats don't lose money from decreased productivity at work, pain definitely impacts the 'earning power' of production animals by decreasing weight gain, milk production or hair/wool quality. Furthermore, whether the animal is involved in production or is a pet, pain causes a negative impact on the quality of life and can lead to 'suffering', which is a condition that we vowed to alleviate when we took the veterinarian's oath. And, because the pain pathway in the animals that we treat is very similar to the pain pathway in the animals that we are, we know that, at the very least, there are physical and physiologic changes that occur across mammalian species. In fact, many of the models developed to evaluate chronic pain in humans actually use animal species and we can use these models to both assure ourselves that animals do indeed feel pain and to enhance our knowledge of pain in our veterinary patients. For instance, we know physiologically that untreated pain causes physical and physiologic changes in both the peripheral and central nervous system and that these changes perpetuate the pain state in both animals and humans.

How do we know when our patients are in pain?

Out patients are masters at hiding pain and don't always manifest discomfort in the presence of humans. If the presence of pain is in question, we should 'ask' the patient if it is in pain by using a dose of analgesic drugs and monitoring the response.

Treatment of chronic pain generally requires multimodal therapy. Multimodal therapy generally provides more effective analgesia, often at lower dosages of drugs, than unimodal therapy. Multimodal therapy can include multiple drug classes and/or nonpharmacologic modes of treatment.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic drugs in all mammals. They are relatively safe, easy to administer, have a fairly long duration of action and treat inflammation as well as pain. Although side effects are always concerning with any drug, NSAIDs actually have a fairly low incidence of side effects and a favorable benefit-to-risk ratio. NSAIDs are ideal for treating many, if not most, of our painful patients since most of the painful conditions that we treat are painful because of inflammation. Certainly, pain from surgery, trauma, musculoskeletal injuries, and osteoarthritis (OA) all involve pain of inflammation. Thus, NSAIDs are among the only drugs that treat not only the pain itself, but also the source of pain. Although newer NSAIDs, like the coxib class of NSAIDs, have not resulted in fewer side effects or more effective control of pain in all patients, the addition of new NSAIDs has provided more options for treatment and this is important since the response to all drugs, including NSAIDs, is different from patient to patient. The possibility to apply NSAIDs by different routes, eg, topically with diclofenac, also expands the treatment options.

What options are available when the patient is unable to take NSAIDS or, more commonly, when the pain advances to a pain state that is uncontrollable by NSAIDs used alone? In that instance, opioids, N-methyl-D-aspartate (NMDA) antagonists, and novel drugs like gabapentin should all be considered as potential therapies. In addition, non-pharmacologic therapies (eg, acupuncture, massage, physical therapy, TENS, etc…) should be strongly considered.